Human leukocyte elastase (HLE) is a member of the family of serine proteases. It is carried by the azurophilic granules of human polymorphonuclear leukocytes and released into the extracellular space. Elastase, like other serine proteases, have a catalytic triad composed of three juxtaposed amino acid residues :aspartate (Asp-102), histidine (His-57), and serine (Ser-195). Through either a "charge relay" or a "proton relay" mechanism, the three residues catalyze a proton extraction via oxyanion attack (ser-195) on an amide carbonyl group. The end result of this reaction is a degradation of peptide bonds.
Under normal conditions, the proteolytic activity of HLE is controlled by several natural protease inhibitors. The primary guardian against connective tissue destruction is .alpha.-1 protease inhibitor (.alpha.-PI). Although .alpha.-PI associates with HLE very quickly and irreversibly, several pathological conditions may arise when .alpha.-PI levels are genetically low, or when .alpha.-PI has been oxidized or degraded, or when access to HLE is restricted. The disease states resulting from uncontrolled elastase activity include: pulmonary emphysema, rheumatoid arthritis, adult respiratory distress syndrome (ARDS), cystic fibrosis, and other related syndromes.